Halopropargyl acyl compound, compositions, microbicidal uses and processes of preparation

ABSTRACT

Compounds of the formula ##STR1## wherein A is selected from the group consisting of (1) phenyl, (2) naphthyl, (3) phenyl substituted with one or more halo, cyano, (C 1  -C 4 )alkyl, nitro, (C 1  -C 4 )haloalkyl, and (C 1  -C 4 )thioalkyl, (4) naphthyl substituted with one or more halo, cyano, (C 1  -C 4 ) alkyl, nitro, (C 1  -C 4 )haloalkyl, and (C 1  -C 4 )thioalkyl, (5) thiophene, (6) furan, (7) thiophene substituted with one or more substituents selected from halo and nitro, and (8) furan substituted with one or more substituents selected from halo and nitro; 
     R is selected from the group consisting of hydrogen, (C 1  -C 4 )alkyl and substituted or unsubstituted phenyl wherein the substituents are selected from one or more halo, cyano, (C 1  -C 4 )alkyl, nitro, (C 1  -C 4 ) haloalkyl, and (C 1  -C 4 )thioalkyl and 
     R 1  is selected from the group consisting of (C 1  -C 4 ) alkoxy; hydrogen; optionally substituted phenyl wherein the phenyl substituents are selected from the group consisting of halo, cyano, (C 1  -C 4 )alkyl; nitro, (C 1  -C 4 )haloalkyl, and (C 1  -C 4 )thioalkyl; (C 1  -C 8 ) alkyl; and optionally substituted heterocycles wherein said heterocycles are selected from the group consisting of thiophene, furan, imidazole, and triazole, which are optionally substituted with (C 1  -C 3 )alkyl, halo, and nitro; and 
     X is selected from the group consisting of I and Br. 
     the halopropargyl acyl hydrazone compounds of the invention are active microbicides and can be used to control microorganisms.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a divisional of application Ser. No. 528,653, filed May 24, 1990 now U.S. Pat. No. 5,112,382.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to control of microorganisms.

2. Description of the Prior Art

Certain classes of iodopropargyl compounds have been proposed as fungicides or microbicides but no compound within those classes has achieved commerical success.

U.S. Pat. No. 4,616,004 to Edwards discloses fungicidal activity for compounds of the formula ##STR2##

U.S. Pat. No. 4,639,460 to Rose shows compounds of the formula ##STR3## as fungicides.

U.S. Pat. No. 4,520,023 to Schmitt shows 3-(3-iodopropargyl)benzo-1,2,3-triazolin-4-ones and their use as microbicidal agents.

There was no suggestion in the prior art that compounds within the formula of the present invention would have utility in controlling microorganisms.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide new compounds for controlling microorganisms.

A further object is to provide methods of making such compounds, methods of using them, compositions comprising such compounds, and uses of such compositions.

These objects, and others which will become apparent from the following disclosure, are achieved by the present invention which comprises in one aspect compounds of the formula ##STR4## wherein A is selected from the group consisting of (1) phenyl, (2) naphthyl, (3) phenyl substituted with one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl, (4) naphthyl substituted with one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl, (5) thiophene, (6) furan, (7) thiophene substituted with one or more substituents selected from halo and nitro, and (8) furan substituted with one or more substituents selected from halo and nitro.

R is selected from the group consisting of hydrogen, (C₁ -C₄)alkyl and substituted or unsubstituted phenyl wherein the substituents are selected from one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl;

R¹ is selected from the group consisting of (C₁ -C₄)alkoxy; hydrogen; optionally substituted phenyl wherein the phenyl substitutents are selected from the group consisting of halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl; (C₁ -C₈)alkyl; and optionally substituted heterocycles wherein said heterocycles are selected from the group consisting of thiophene, furan, imidazole, and triazole, which are optionally substituted with (C₁ -C₃)alkyl, halo, and nitro; and

X is selected from the group consisting of I and Br.

In another aspect the invention comprises a method of preparing such compound comprising reacting a compound of the formula ##STR5## with an iodinating or brominating agent.

A further aspect comprises using a composition comprising the compounds, or the compound itself, to protect a material selected from the group consisting of wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENT

The compounds of the invention are of formula I as set forth above. The more preferred embodiments are the following compounds:

1. N'-Methoxycarbonyl-N'-3-bromopropargyl 4-chlorobenzaldehyde hydrazone

2. N'-Formyl-N'-3-bromopropargyl 4-chlorobenzaldehyde hydrazone

3. N'-Methoxycarbonyl-N'-3-iodopropargyl benzaldehyde hydrazone

4. N'-Methoxycarbonyl-N'-3-iodopropargyl 4-methylbenzaldehyde hydrazone

5. N'-Methoxycarbonyl-N'-3-iodopropargyl 4-chlorobenzaldehyde hydrazone

6. N'-Benzoyl-N'-3-iodopropargyl benzaldehyde hydrazone

7. N'-Methoxycarbonyl-N'-3-bromopropargyl 4-fluorobenzaldehyde hydrazone

8. N'-Methoxycarbonyl-N'-3-iodopropargyl 5-nitro-2-furancarboxaldehyde hydrazone

9. N'-Methoxycarbonyl-N'-3-iodopropargyl 4-cyanobenzaldehyde hydrazone

10. N'-Methoxycarbonyl-N'-3-iodopropargyl 4-fluorobenzaldehyde hydrazone

11. N'-Methoxycarbonyl-N'-3-iodopropargyl 3,4-dichlorobenzaldehyde hydrazone

12. N'-Benzoyl-N'-3-iodopropargyl 3-nitrobenzaldehyde hydrazone

13. N'-Ethoxycarbonyl-N'-3-iodopropargyl 3,4-dichlorobenzaldehyde hydrazone

14. N'-Ethoxycarbonyl-N'-3-bromopropargyl 3,4-dichlorobenzaldehyde hydrazone

15. N'-Methoxycarbonyl-N'-3-iodopropargyl 3,5-dichlorobenzaldehyde hydrazone

16. N'-Methoxycarbonyl-N'-3-bromopropargyl 3,5-dichlorbenzaldehyde hydrazone

The iodopropargyl compounds, i.e., those wherein X is I, are preferred.

As stated above, compositions comprising a compound according to formula I and either an agronomically acceptable carrier, a cosmetic agent, a cutting oil, a soap or synthetic detergent, a stabilizer, a film-forming material, or the like have a wide range of utility for protecting against or controlling microorganisms from a wide variety of classes including fungus, bacteria, algae, viruses and yeasts. The preferred utilities of the compositions are to protect wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.

The following lists specific industries and applications of the compounds or compositions:

    ______________________________________                                         Industry           Application                                                 ______________________________________                                         Adhesives, sealants                                                                               adhesives                                                                      caulks                                                                         sealants                                                    Agriculture/food chain                                                                            adjuvant preservation                                                          agricultural active ingredient                                                 agricultural chemical                                                          preservative                                                                   agricultural formulations                                                      preservation                                                                   animal feed preservation                                                       dairy chemicals                                                                fertilizer preservation                                                        food preservation                                                              food processing chemicals                                                      grain preservation                                                             post-harvest produce                                                           protection                                                                     sugar processing                                                               tobacco                                                     Construction products                                                                             asphalt/concrete                                                               cement modifiers                                                               construction products                                                          roof mastics                                                                   synthetic stucco                                                               wall mastics                                                                   joint cement                                                Cosmetics and toiletries                                                                          cosmetics                                                                      raw materials for cosmetics,                                                   toiletries                                                                     toiletries                                                  Disinfectants, antiseptics                                                                        antiseptic                                                                     disinfectant                                                Emulsions, dispersions                                                                            aqueous dispersions                                                            dispersed pigments                                                             latex                                                                          photographic emulsions                                                         pigment slurries                                                               polymer latices                                             Formulated consumer & industrial                                                                  air fresheners                                              products           fabric softeners                                                               hand cleaners                                                                  polishes, floor, furniture,                                                    shoe                                                                           sponges & towelettes                                                           spray starch                                                                   waxes                                                       Industrial processing, misc                                                                       dry cleaning fluids                                                            preservation                                                                   electrodeposition paint,                                                       baths, rinses.                                                                 electrodeposition pre-                                                         treatment, post rinses                                                         industrial fluids preservation                                                 pasteurization baths                                                           process aid preservation                                    Industrial water treatment                                                                        air washers                                                                    cooling towers                                                                 cooling water                                                                  water cooling                                               Laundry            household laundry products                                                     laundered goods                                                                laundry wash water                                                             pre-washers                                                                    sanitizers-laundry                                                             removers, spot & stain                                      Leather, leather products                                                                         leather and hide                                                               leather and hide products                                   Lubricants, hydraulic aids                                                                        automotive lubricants and                                                      fluids                                                                         conveyor lubricants                                                            greases                                                                        hydraulic fluids                                                               hydraulic oils                                                                 lubricants                                                  Medical devices    diagnostic enzymes                                                             diagnostic kits                                                                medical devices                                             Metalworking & related app's                                                                      cutting fluids                                                                 metal cleaning                                                                 metalworking fluids                                         Odor control (active ingredient)                                                                  air conditioning                                                               animal bedding                                                                 cat litter                                                                     chemical toilet prep'ns                                                        deodorizers                                                                    humidifiers                                                                    industrial deodorants                                                          sanitary formulations                                                          toilet bowls                                                Paints and coatings                                                                               coating emulsions                                                              paints                                                      Paper and wood pulp, their                                                                        absorbant materials of paper                                products           and wood pulp                                                                  packaging materials of paper                                                   and wood pulp                                                                  paper                                                                          paper products                                                                 paper treatment                                                                soap wrap                                                                      wood pulp                                                                      wood pulp products                                          Paper mill         paper mill slimicides                                                          pulp and paper slurries                                     Petroleum refining, fuels                                                                         aviation fuels (jet fuel,                                                      aviation gas)                                                                  burner, diesel and turbine                                                     fuel oils                                                                      coal slurries                                                                  diesel fuel additives                                                          diesel fuels                                                                   fuels                                                                          gasoline                                                                       heating oils                                                                   hydrocarbons                                                                   kerosene                                                                       liquefied petroleum gas                                                        petrochemical feedstocks                                                       petroleum products, storage,                                                   transportation and                                                             production                                                                     recycled petroleum products                                                    residual fuel oils                                                             turbine oils                                                Photographic chemicals and process                                                                photographic processing -                                                      wash water, rinses                                                             photoplate processing                                                          chemicals (developers,                                                         stabilizers etc)                                            Printing           fountain solutions (printing)                                                  ink components (pigments,                                                      resins, solvents, etc)                                                         inks                                                        Sanitizers (active)                                                                               sanitizers                                                                     sanitizers-dairy                                                               sanitizers-dental                                                              sanitizers-fermentation                                                        sanitizers-food preparation                                                    sanitizers-food processing                                                     sanitizers-medical                                                             sanitizers-rendering                                                           sanitizers-veterinary                                       Soaps, detergents, cleaners                                                                       cleaners                                                                       detergents, hand automatic                                                     laundry, other                                                                 household cleaners                                                             industrial cleaners                                                            liquid soaps, hand, dish,                                                      laundry                                                                        oil and grease remover                                                         powdered soaps                                                                 raw materials for cleaning                                                     products                                                                       soaps                                                                          surfactants                                                 Textiles, textile products                                                                        bonded fabrics                                                                 burlap                                                                         canvas                                                                         canvas goods                                                                   carpet backing                                                                 carpets                                                                        clothing                                                                       coated fabrics                                                                 curtains                                                                       draperies                                                                      engineering textiles                                                           fibers                                                                         geotextiles                                                                    goods made of textiles                                                         knitted fabrics                                                                nets                                                                           nonwoven fabrics                                                               rope                                                                           rugs                                                                           textile accessories                                                            textile products                                                               textiles                                                                       upholstery                                                                     woven fabrics                                                                  yarn                                                        Textile processing dye fixatives                                                                  dyes                                                                           fiber lubricants                                                               hand modifiers                                                                 sizes                                                                          textile processing fluids                                   Therapeutic (active or                                                                            animal health/veterinary                                    preservative)      aquaculture                                                                    dental                                                                         human health                                                                   pharmaceutical/therapeutic                                  Water purification charcoal beds                                                                  deionization resins                                                            filters                                                                        membranes                                                                      reverse osmosis membranes                                                      ultrafilters                                                                   water purification                                                             water purification pipes,                                                      tubing                                                      Wood applications  lazures (wood stains)                                                          wood                                                                           wood products                                               Miscelleneous      alcohols                                                                       bedding incorporating water                                                    or gels                                                                        ceramic                                                                        contact lens cases-leaching                                                    electronic circuitry                                                           electronics chemicals                                                          enzymes-food production                                                        enzymes-industrial                                                             gel cushions                                                                   laboratory reagents                                                            marine antifoulants                                                            mildewcides                                                                    mining applications                                                            natural rubber latex                                                           oil field applications                                                         pipes                                                                          plastics                                                                       polymer systems                                                                polymers and resins                                                            (synthetic and natural)                                                        reagent preservation                                                           rubber                                                                         rubber products                                                                skin remover                                                                   solid protective/decorative                                                    films                                                                          swimming pools                                                                 waste treatment                                                                water beds                                                  ______________________________________                                    

The amounts of the compound to be used depend on the application. The useful amounts for a particular application are similar to amounts used for other microbicide compounds.

The compound can be used in combination with other microbicides. The term "microbicide" is considered equivalent to "antimicrobial" as used herein.

Compounds of formula I can be prepared by a variety of methods. One suitable method comprises reacting a compound of formula II with an iodinating or brominating agent.

Suitable iodinating or brominating agents include, for example, iodine, bromine, an iodine-amino compound such as morpholineiodine complex, morpholine-bromine complex, N-bromosuccinimide ("NBS") and N-iodosuccinimide ("NIS"), the latter being the most preferred.

When an iodine, bromine, or iodo-amino compound is used, base should also be used, preferably sodium or potassium hydroxide, and solvent such as methanol, ethanol, and aqueous ethanol should also be used.

When NIS or NBS is used, a catalyst such as, for example, silver nitrate, or the like, should be used in presence of solvent such as acetone, methyl ethyl ketone, tetrahydrofuran, and the like.

Reaction times of about 20 minutes to about 24 hours have been utilized successfully with reaction temperatures of about 0° C. to about 25° C.

Suitable methods of application of compounds of formula I to control fungi, bacteria, algae, viruses, yeasts, and the like are in amounts and with carriers, etc., as well known in the art.

The following examples are presented to illustrate a few embodiments of the invention. All parts and percentages are by weight unless otherwise indicated.

Table (1) shows the structures and the physical data of the preferred representative compounds.

                  TABLE 1                                                          ______________________________________                                         Physical Data                                                                   ##STR6##                                                                      NO.     A           R'       X   Melting Point                                 ______________________________________                                         1       4-Cl-Ph     OMe      Br  102-105° C.                            2       4-Cl-Ph     H        Br  135-140° C.                            3       Ph          OMe      I   149-151° C.                            4       4-Me-Ph     OME      I   112-116° C.                            5       4-Cl-Ph     OMe      I   143-146° C.                            6       Ph          Ph       I   109-111° C.                            7       4-F-Ph      OMe      Br  86-91° C.                              8       5-NO.sub.2 -furan                                                                          OMe      I   --                                            9       4-CN-Ph     OMe      I   126-132° C.                            10      4-F-Ph      OMe      I   --                                            11      3,4-Cl.sub.2 -Ph                                                                           OMe      I   110-118° C.                            12      3-NO.sub.2 Ph                                                                              Ph       I   139-145° C.                            13      3,4-Cl.sub.2 -Ph                                                                           OEt      I   169-170° C.                            14      3,4-Cl.sub.2 -Ph                                                                           OEt      Br  148-149° C.                            15      3,5-Cl.sub.2 -Ph                                                                           OMe      I   183-184° C.                            16      3,5-Cl.sub.2 -Ph                                                                           OMe      Br  141-142°  C.                           ______________________________________                                    

EXAMPLE 1 Preparation of N'-methoxycarbonyl-N'-3-bromopropargyl 4-chlorobenzaldehyde hydrazone

To the suspension of N'-methoxycarbonyl 4-chlorobenzaldehyde hydrazone (4.0 g, 0.0188 mole) in dry acetone (50 ml) at room temperature under nitrogen was added potassium carbonate (3.9 g, 0.028 mole), followed by propargyl bromide (3.4 g, 0.028 mole) with magnetic stirring. The reaction mixture was refluxed for 24 hr. The reaction mixture was cooled down to room temperature and was poured into water (200 ml). The resultant precipitate was collected by suction-filtration affording 4.7 g (99% yield) of N'-methoxycarbonyl-N'-propargyl 4-chlorobenzaldehyde hydrazone, m.p.=102°-105° C. An NMR spectrum showed the desired compound.

This intermediate was used for the next step without further purification.

To the suspension of N'-methoxycarbonyl-N'-propargyl 4-chlorobenzaldehyde hydrazone (1.25 g, 0.005 mole) in dry acetone (40 ml) at room temperature with magnetic stirring was added N-bromo-succinimide (1.03 g, 0.0058 mole), followed by silver nitrate (0.011 g, 0.00065 mole). The reaction mixture was stirred at room temperature for 1 hr. The purple reaction mixture was poured into water and the resultant precipitate was collected by suction-filtration to give a crude product. The crude product was dissolved in ethyl acetate (50 ml), dried over anhydrous sodium sulfate, and filtered to get a colorless solution. The solvent was evaporated on a rotary evaporator affording 1.10 g (67.1% yield) of N'-methoxycarbonyl-N'-3-bromopropargyl 4-chloro-benzaldehyde hydrazone as a solid. m.p.=102°-105° C. An NMR spectrum showed the desired compound.

EXAMPLE 2 Biocidal Evaluations of Compounds

A minimum inhibitory concentration (MIC) value is obtained using a broth, two-fold serial dilution test performed as follows: A stock solution or dispersion of the test compound, typically at a concentration of 1%, is made in a 5:3:2 solvent solution of acetone, methanol, and water. A volume of the stock solution is dispensed into culture media to give an initial starting test concentration of 500 ppm compound.

The test is carried out by adding an equal volume of broth to each vessel in the dilution series, escept for the first vessel. The first vessel contains twice the volume of broth plus the initial concentration of test compound. One half of the broth from the first vessel is transferred to the second vessel. After being mixed, one half the resulting volume is removed from the second vessel and transferred to the third vessel. The entire cycle is repeated sufficiently to give a series of concentrations amounting to 500, 250, 125, 63, 31, 16, 8, and 4 ppm (or 100, 50, 25, 12.5, 6.2, 3.1, 1.6, and 0.8), respectively.

Each vessel is then inoculated with a cell suspension of the appropriate test organism. Bacteria are grown in broth and fungi on agar slants for a time and at a temperature appropriate to the species being tested. At the end of the growth period, the broth is vortexed to disperse the cells. In the case of fungi, the spores are harvested by pipetting water onto the slant and dislodging the spores with a sterile loop. The cell/spore suspension is standardized by controlling incubation time, temperature, and the volume of the diluent. The suspension is then used to inoculate the vessels containing the broth compound. The vessels are then incubated at the appropriate temperature. After the incubation, the vessels are examined for growth/no growth. The minimum inhibitory concentration (MIC) is defined as the lowest concentration of compound that results in complete inhibition of growth of the test organism.

The organisms tested to demonstrate biocidal activity include:

BACTERIA:

Pseudomonas fluorescens (Psfl)

Pseudomonas aerugenosa (Psae)

Escherichia coli (Ecol)

Staphylococcus aureus (Saur)

FUNGI:

Aspergillus niger (Anig)

Aureobasidium pullulans (Apul)

                  TABLE 2                                                          ______________________________________                                         Biocidal Evaluation                                                            The Result of Minimum Inhibitory Concentration (MIC) Tests                     Compound                                                                               MIC (ppm)                                                              #       Psfl    Psae    Ecol  Saur  Anig  Apul                                 ______________________________________                                         1       >500     250    >500  >500  >500   63                                  2       >500     250    >500  >500  >500   63                                  3       >500     250    >500   125   <4   <4                                   4        125     125     250    16   <4    8                                   5        125      16     125    8    <4   <4                                   6         50      25      50    50    6    3                                   7        125      31     125    63    31   31                                  8        250     125      63   <4    <4   <4                                   9       >500    >500    >500  >500  >250  --                                   10      >500    >500    >500   <4    <4   <4                                   11      >500    >500    >500    8    <4   <4                                   12      >100    >100    >100  >100  >100  100                                  13      >100    >100    >100  >100   100  >100                                 14      >100    >100    >100  >100  >100  >100                                 15      >100    >100    >100  >100  >100  >100                                 16      >100    >100    >100  >100  >100  >100                                 ______________________________________                                    

EXAMPLE 3 In-Vitro Plant Fungicide Tests of Compounds

The organisms employed in the test are:

PYU Pythium ultimum (Oomycete)

PHY Phytophthora capsici (Oomycete)

PIR Piricularia oryzae (Ascomycete)

HEL Cochliobolus sativus (Ascomycete)

BOC Botrytis cinerea (Ascomycete)

FUS Fusarium roseum (Ascomycete)

SEP Septoria nodorum (Ascomycete)

RHI Rhizoctonia solani (Basidiomycete)

XAN Xanthomonas campestris (bacterium)

Methods:

1. Culture maintenance: Transfers in steps 1 and 2 are done in a laminar flow hood. All 8 fungi and the bacterium used in this test are transferred and maintained on potato dextrose agar plates each week (2 plates/organism). Organisms are used when they are the following ages: a. 1 week old: PYU, PHY, RHI; b. 2 weeks old: XAN, PIR, BOC, HEL, FUS, SEP, COL, MON, CER, UST, ALT; c. 3 weeks old: PSH, VEN. Pythium ultimum and Phytophthora capsici are transferred to asparagine-sucrose broth shake cultures (ASB). Rhizoctonia solani, Fusarium roseum, and Zanthomonas campestris are mainted in yeast extract-dextrose broth (YDB) on a shaker. Culture flasks are inoculated with 6 mycelial plugs each (except for Pythium which is inoculated with only 3 plugs) taken from PDA plates. All liquid shaker cultures are used after 2 days growth.

2. Inoculum preparation. Conidia and mycelium from PIR, BOC, HEL, SEP, COL, MON, CER, PSH, UST and ALT are lightly scraped off into YDB so that mostly conidia are used as inoculum. The conidial suspension is strained through a double layer of cheesecloth to remove mycelial clumps. One plate produces enough conidia or mycelium to inoculate 100 ml of YDB. XAN broth culture is poured (1 ml culture/100 ml broth) into YDB, PYU, PHY, RHI and FUS cultures are ground up (2-3 5 second bursts in a blender) and all but Pythium and Phytophthora are filtered through a double layer of sterile cheesecloth to remove large mycelial clumps. Ten ml of the culture solutions of R. solani and F. roseum are added to 90 ml of YSB and 10 ml of the P. capsici is added to 90 ml ASB. Two ml of the culture solution of P. ultimum is added to 98 ml of ASB. Care must be made not to overinoculate (e.g. solutions should appear fairly clear to the eye, yet when held up to light a faint cloudiness should be visible) or standards will not behave properly. The inoculum mixtures are placed in microtiter plates using a 12-tipped pipet. 175 μl (single dose) or 100 μl (dose-response test) of inoculum broth is placed in each well of the microtiter plates. The plates with inoculated media are placed in the refrigerator overnight. There are two replications per treatment.

3. Addition of compounds. This operation is carried out in a chemistry hood. Six microtiter plates have 245 microliters of sterile water added to their wells ahead of time. 10 Mg a.i. of the compounds are placed in 1 ml 1:1 acetone:methanol. 5 Microliters of this solution is pipetted into the microtiter plates containing the sterile water according to the grid. There are 45 compounds and 3 scattered control treatments per plate. There are 2 replicates per treatment. 25 Microliters of solution is transferred to the inoculated plates with a 96 well replicator. The replicator is flame sterilized with alcohol, rinsed with sterile water, and blotted on sterile paper towells between each transfer.

                                      TABLE 3                                      __________________________________________________________________________     The Results of In-Vitro Plant Fungicide Tests                                  Rate      % Control                                                            Compound                                                                             (PPM)                                                                              BOX                                                                               FUS HEL PHY PIR                                                                               PYU RHI SEP                                                                               XAN                                     __________________________________________________________________________     1     25  0  0   0   0    0 0    0  -- 0                                       2     25  0  0   0   75   50                                                                               0    0  -- 0                                       3     25  0  75  0   75   0 75  100 -- 0                                             50  0  100 0   100  95                                                                               100 100  75                                                                               0                                       4     --  -- --  --  --  -- --  --  -- --                                      5     25  0  95  100 50  100                                                                               50   75 -- 0                                       6     25  0  0   0   100 100                                                                               100  0  100                                                                               0                                       7     25  0  0   0   0    0 0    0  100                                                                               0                                             50  0  0   0   90   90                                                                               100  0   0 0                                       8     50  0  100 100 100 100                                                                               100 100 100                                                                               0                                             50  0  100 100 0   100                                                                               --  100 100                                                                               0                                       9     50  50 100 100 95  100                                                                               100 100 100                                                                               0                                       10    50  0  100 100 100 100                                                                               100 100 100                                                                               0                                       11    50  50 100 100 90  100                                                                               0   100  90                                                                               0                                       12    50  0  0   0   0   100                                                                               0    95  0 0                                       13    25  0  75  50  0   100                                                                               0    90  50                                                                               0                                       14    25  0  0   0   0    0 0    50  0 0                                       15    25  0  75  50  0   100                                                                               0    75  0 0                                       16    25  0  0   0   0    0 0    0   0 0                                       __________________________________________________________________________

EXAMPLE 6 Agricultural Fungicide Evaluations of Compounds

The compounds of this invention were tested for fungicidal activity in vivo against cucumber downy mildew (CDM), rice blast (RB), rice sheath blight (RSB), tomato late blight (TLB), wheat powdery mildew (WPM), wheat stem rust (WSR) and wheat leaf rust (WLR) and the results are shown in Table 4. In tests on cereals (except for rice plants used for testing rice blast), the plants were trimmed about 24 hours prior to the application of the fungicide compound to provide a uniform plant height and to facilitate uniform application of the compound and inoculation with the fungus. The compounds were dissolved in a 2:1:1 mixture of water, acetone, and methanol, sprayed onto the plants, allowed to dry (four to six hours), and then the plants were inoculated with the fungus. Each test utilized control plants which were sprayed with the water, acetone, and methanol mixture and inoculated with the fungus. The remainder of the technique of each of the tests is given below and the results are reported as percent disease control (percentages of plants treated with the compounds of the present invention lacking disease signs or symptoms compared to the untreated control plants).

Cucumber Downy Mildew (CDM):

Pseudoperonospora cubensis was maintained on leaves of live Marketer cucumber plants in a constant temperature room at 65° F. to 75° F. in humid air with moderate light intensity for 7 to 8 days. A water suspension of the spores from infested leaves was obtained and the spore concentration was adjusted to about 100,000 per ml of water.

Marketer cucumber seedlings were inoculated by spraying the underside of the leaves with a DeVilbiss atomizer until small droplets were observed on the leaves. The inoculated plants were incubated in a mist chamber for 24 hours at about 70° F. and then subsequently incubated for 6 to 7 days in a controlled temperature room under mist at 65° F. to 75° F. Seven days after inoculation, the percent disease control was determined.

Rice Blast (RB):

Nato rice plants were inoculated with Piricularia oryzae (about 20,000 conidia per ml) by spraying the leaves and stems with an airbrush until a uniform film of inoculum was observed on the leaves. The inoculated plants were incubated in a humid environment (75° F. to 85° F.) for about 24 hours, then placed in a greenhouse environment (70° F. to 75° F.). Seven to eight days after inoculation, the percent disease control was determined.

Rice Sheath Blight (RSB):

Pellicularia filamentosa (f. sp. sasiki) was cultured on an autoclaved mixture of crushed rice seeds and potato dextrose broth (100 gms of rice seeds per 30 ml of potato dextrose broth) in a 500 ml Erlenmeyer flask. After 10 days, the culture was blended in a blender to produce a uniform inoculum. Approximately one teaspoon of inoculum was spread among Lebonnet rice seedlings on the soil surface of each pot (3 inch diameter). The inoculated seedlings were incubated for 5 days in a humidity cabinet (85° F. to 90° F.). Percent disease controls were determined immediately after removing the seedlings from the cabinet.

Tomato Late Blight (TLB):

Phytophthora infestans was cultured on four week old Pixie tomato plants in a controlled environment room (65° F. to 70° F. and 100% relative humidity). After storage, the spores were washed from the leaves with water and dispersed by DeVilbiss atomizer over three week old Pixie tomato plants which had been sprayed previously with experimental fungicides. The inoculated plants were placed in a humidity cabinet at 70° F. and constant mist for 24 hours for infection. The plants were then moved to the controlled environment room as above and scored after three more days incubation. Disease control levels were recorded as percent control four days after inoculation and five days after spraying the compounds.

Wheat Powdery Mildew (WPM):

Erysiphe graminis (f. sp. tritici) was cultured on Pennol wheat seedlings in a controlled temperature room at 65° F. to 75° F. Mildew spores were shaken from the culture plants onto Pennol wheat seedlings which had been sprayed previously with the fungicide compound. The inoculated seedlings were kept in a controlled temperature room at 65° F. to 75° F. and subirrigated. The percent disease control was rated 8 to 10 days after the inoculation.

Wheat Stem Rust (WSR):

Puccinia graminis (f. sp. tritici Race 15B-2) was cultured on Wanzer wheat seedlings for a period of 14 days in a greenhouse. A water suspension of the spores from infested plants was obtained and the spore concentration was adjusted to about 200,000 spores per ml of deionized water. Wanzer wheat plants which had been previously treated with the fungicide compounds were inoculated by applying the stem rust spore suspension, until runoff, with a DeVilbiss atomizer at 5 lbs. per square inch air pressure. After inoculation, the plants were placed in a humid environment at approximately 75° F. where they were exposed to 12 hours of continuous darkness followed by a minimum of 3 to 4 hours of light having an intensity of about 500 footcandles. The temperature in the chamber did not exceed 85° F. At the end of the light period, the plants were placed in a greenhouse where they were permitted to grow for a period of two weeks at which time the percent disease control was determined.

Wheat Leaf Rust (WLR):

Puccinia recondita (f. sp. tritici Races PKB and PLD) was cultured on seven day old wheat (cultivar Fielder) over a 14 day period in the greenhouse. Spores were collected from the leaves with a cyclone vacuum or by settling on aluminum foil. The spores were cleaned by sieving through a 250 micron opening screen and stored or used fresh. Storage employed sealed bags in an Ultralow freezer. When stored, spores must be heat shocked for two minutes at 40° F. before use. A spore suspension is prepared from dry uredia by adding 20 mg (9.5 million) per ml of Soltrol oil. The suspension is dispensed into gelatin capsules (0.7 ml capacity) which attach to the oil atomizers. One capsule is used per flat of twenty of the two inch square pots of seven day old Fielder wheat. After waiting for at least 15 minutes for the oil to evaporate from the wheat leaves, the plants are placed in a dark mist chamber (18°-20° C. and 100% relative humidity) for 24 hours. The plants are then put in the greenhouse for the latent period and scored after 10 days for disease levels. Protective and curative tests were inoculated one day after and two days, respectively, before spraying the plants with the test chemicals.

                  TABLE 4                                                          ______________________________________                                         Green House Test Results of Plant diseases Control                             Com-   Rate    % Control                                                       pound  (ppm)   CDM     RB   SNW   TLB  WLR   WPM                               ______________________________________                                         1      --      --      --   --    --   --    --                                2      600     --      --   --    50   0     0                                 3      200     99      90   --    80   50    50                                4      200     95      90   50    80   50    0                                 5      200     99      95   0     90   80    0                                 6      --      --      --   --    --   --    --                                7      200      0       0   0     0    0     0                                 8      200      0      90   0     0    0     0                                 9      200     85       0   0     0    0     0                                 10     200     50      50   0     0    0     50                                11     200     95      90   0     80   --    0                                 12     --      --      --   --    --   --    --                                13     200     85       0   0     0    50    50                                14     200      0       0   0     0    0     85                                15     200      0       0   0     0    0     0                                 16     200      0       0   0     0    0     0                                 ______________________________________                                     

What is claimed is:
 1. Composition comprising (A) a compound of the formula ##STR7## wherein A is selected from the group consisting of (1) phenyl, (2) naphthyl, (3) phenyl substituted with one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalky, and (C₁ -C₄)thioalkyl, (4) naphthyl substituted with one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl, (5) thiophene, (6) furan, (7) thiophene substituted with one or more substituents selected from halo and nitro, and (8) furan substituted with one or more substituents selected from halo and nitro;R is selected from the group consisting of hydrogen, (C₁ -C₄)alkyl and substituted or unsubstituted phenyl wherein the substituents are selected from one or more halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl; R¹ is selected from the group consisting of (C₁ -C₄)alkoxy; hydrogen; optionally substituted phenyl wherein the phenyl substitutents are selected from the group consisting of halo, cyano, (C₁ -C₄)alkyl, nitro, (C₁ -C₄)haloalkyl, and (C₁ -C₄)thioalkyl; (C₁ -C₈) alkyl; and optionally substituted heterocycles wherein said heterocycles are selected from the group consisting of thiophene, furan, imidazole, and triazole, which are optionally substituted with (C₁ -C₃)alkyl, halo, and nitro; and X is selected from the group consisting of I and Br;and (B) a component selected from the group consisting of a cosmetic agent, a cutting oil, a soap, a synthetic detergent, and a film-farming material.
 2. Composition according to claim 1 wherein A is selected from the group consisting of phenyl, phenyl substituted with halo or nitro, and furan substituted with nitro.
 3. Composition according to claim 2 wherein X is I.
 4. Composition according to claim 1 wherein R is hydrogen and R¹ is selected from the group consisting of hydrogen, (C₁ -C₄)alkoxy, and phenyl.
 5. Composition according to claim 1 wherein A is selected from the group consisting of phenyl, phenyl substituted with halo or nitro, and furan substituted with nitro; R is hydrogen; R¹ is selected from the group consisting of hydrogen, (C₁ -C₄)alkoxy, and phenyl; and X is I.
 6. Composition according to claim 1 selected from the group consisting of N'-methoxycarbonyl-N'-3-bromopropargyl 4-chlorobenzaldehyde hydrazone; N'-formyl-N'-3-bromopropargyl 4-chlorobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl benzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 4-methylbenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 4-chlorobenzaldehyde hydrazone; N'-benzoyl-N'-3-iodopropargyl benzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-bromopropargyl 4-fluorobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 5-nitro-2-furancarboxaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 4-cyanobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 4-fluorobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 3,4-dichlorobenzaldehyde hydrazone; N'-benzoyl-N'-3-iodopropargyl 3-nitrobenzaldehyde hydrazone; N'-ethoxycarbonyl-N'-3-iodopropargyl 3,4-dichlorobenzaldehyde hydrazone; N'-ethoxycarbonyl-N'-3-bromopropargyl 3,4-dichlorobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-iodopropargyl 3,5-dichlorobenzaldehyde hydrazone; N'-methoxycarbonyl-N'-3-bromopropargyl 3,5-dichlorbenzaldehyde hydrazone.
 7. Process for controlling microorganisms comprising applying or incorporating in a locus, a microbicidally effective amount of a composition according to claim
 1. 8. Process for controlling fungi comprising applying or incorporating in a locus a fungicidally effective amount of a composition according to claim
 1. 9. Process for controlling bacteria comprising applying or incorporating in a locus a bactericidally effective amount of a composition according to claim
 1. 10. Process for controlling algae, viruses or yeasts comprising applying or incorporating in a locus an effective amount of a composition according to claim
 1. 11. Process for protecting a material selected from the group consisting of wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms comprising applying to or incorporating in said material a microbicidally effective amount of a composition according to claim
 1. 